Journal of Clinical Research & Bioethics

Abstract

Advancing Dose-Finding Trials: A Review of the Modified Huber Loss Function for Continual Reassessment Methods

Fangfang Jiang, Emine O. Bayman and Gideon K. D. Zamba*

Phase I Dose-Finding (DF) trials struggle to balance efficacy and toxicity, often relying on the Traditional Escalation Rule (TER) or “3+3” design, which is criticized for ignoring dose-toxicity information. Continual Reassessment Methods (CRM) improve upon TER using Bayesian frameworks but focus mainly on mean posterior toxicity estimates, neglecting distribution uncertainties. GMHLF combines quadratic and absolute loss functions to handle deviations from target doses and incorporates unequal penalties for underdoing and overdosing, controlled by a tolerance level k. Evaluations show GMHLF accurately identifies the Maximum Tolerated Dose (MTD) with fewer patients than TER and other methods, even when applied to real trial data. The authors suggest exploring asymmetric GMHLFs and developing user-friendly tools to enhance practical applications. Future research should focus on robust methodologies and effective algorithm integration.

Published Date: 2024-07-18; Received Date: 2024-06-13